Supported by Grant HL47678 from NHLBI to Dr. Antzelevitch, and grants from Medtronic Japan to Dr. Emori, the American Heart Association to Drs. Emori and Antzelevitch, and the New York State and Florida Grand Lodges F.&A.M.
Cellular Basis for Complex T Waves and Arrhythmic Activity Following Combined IKr and IKs Block
Article first published online: 13 AUG 2003
© Futura Publishing Company, Inc. 2001
Journal of Cardiovascular Electrophysiology
Volume 12, Issue 12, pages 1369–1378, December 2001
How to Cite
EMORI, T. and ANTZELEVITCH, C. (2001), Cellular Basis for Complex T Waves and Arrhythmic Activity Following Combined IKr and IKs Block. Journal of Cardiovascular Electrophysiology, 12: 1369–1378. doi: 10.1046/j.1540-8167.2001.01369.x
Dr. Emori was awarded first prize in the NASPE Young Investigator Award competition on the basis of this study.
- Issue published online: 13 AUG 2003
- Article first published online: 13 AUG 2003
- Manuscript received 18 July 2001; Accepted for publication 15 October 2001.
- Cited By
- long QT syndrome;
- torsades de pointes;
- M cell;
- ventricular wall
Combined Congenital and Acquired LQTS. Introduction: A growing number of cardiomyopathies have been shown to result in a reduction in both IKr and IKs, yet little is known about the electrophysiologic and ECG characteristics of combined IKr and IKs block.
Methods and Results: To address this gap in our knowledge, transmembrane action potentials (APs) from epicardial, M, and endocardial cells were recorded simultaneously, together with a transmural ECG from arterially perfused canine left ventricular wedge preparations exposed to combined IKr (d-sotalol; 100 μmol/L) and IKs (chromanol 293B; 30 to 60 μmol/L) block. Under baseline conditions, the T wave was typically upright; epicardium repolarized first, coinciding with the peak of the T wave, and the M cells repolarized last, coinciding with the end of the T wave (Tend). Complex (inverted, biphasic, and triphasic) T waves developed following combined IKr and IKs block. M and epicardial APs prolonged dramatically, so that the endocardial AP was now the earliest to repolarize, coinciding with the first nadir of the complex T wave. In the case of biphasic/triphasic or inverted T waves, Tend coincided with repolarization of either M or epicardial cells, whichever was the last to repolarize. QT intervals prolonged from 286 ± 13 msec up to 744 ± 148 msec and transmural dispersion of repolarization (TDR) increased from 33 ± 10 msec up to 244 ± 71 msec. Early afterdepolarizations (EADs) developed in M and epicardial cells, evoking extrasystoles that precipitated polymorphic ventricular tachycardia. Acceleration-induced EADs and T wave alternans also were observed.
Conclusion: Combined IKr and IKs block gives rise to inverted, biphasic, and triphasic T wave morphologies, a dramatic increase in TDR, and a high incidence of EADs. The diversity of T wave morphologies derives from a preferential AP prolongation of different transmural layers leading to variation in the predominance of voltage gradients on either side of the M cell region. Our study provides direct evidence linking EADs that arise in ventricular epicardial and M cells to the triggered beats that precipitate polymorphic ventricular tachycardia. Our results also suggest possible guidelines for the estimation of TDR from complex T waves appearing in the precordial leads of the surface ECG.